Eurosurveillance

BackgroundMitigation of SARS-CoV-2 transmission from international travel is a priority. Travellers from countries with travel restrictions (closed travel-corridors) were required to quarantine for 14 days over Summer 2020 in England. We describe the genomic epidemiology of travel-related cases in England and evaluate the effectiveness of this travel policy. MethodsBetween 27/05/2020 and 13/09/2020, probable travel-related SARS-CoV-2 cases and their contacts were identified and combined with UK SARS-CoV-2 sequencing data. The epidemiology and demographics of cases was identified, and the number of contacts per case modelled using negative binomial regression to estimate the effect of travel restriction, and any variation by age, sex and calendar date. Unique travel-related SARS-CoV-2 genomes in the COG-UK dataset were identified to estimate the effect travel restrictions on cluster size generated from these. The Polecat Clustering Tool was used to identify a travel-related SARS-CoV-2 cluster of infection. Findings4,207 travel-related SARS-CoV-2 cases are identified. 51.2% (2155/4207) of cases reported travel to one of three countries; 21.0% (882) Greece, 16.3% (685) Croatia and 14.0% (589) Spain. Median number of contacts per case was 3 (IQR 1-5), and greatest for the 16-20 age-group (9.0, 95% C.I.=5.6-14.5), which saw the largest attenuation by travel restriction. Travel restriction was associated with a 40% (rate ratio=0.60, 95% C.I.=0.37-0.95) lower rate of contacts. 827/4207 (19.7%) of cases had high-quality SARS-CoV-2 genomes available. Fewer genomically-linked cases were observed for index cases related to countries with travel restrictions compared to cases from non-travel restriction countries (rate ratio=0.17, 95% C.I.=0.05-0.52). A large travel-related cluster dispersed across England is identified through genomics, confirmed with contact-tracing data. InterpretationThis study demonstrates the efficacy of travel restriction policy in reducing the onward transmission of imported cases. FundingWellcome Trust, Biotechnology and Biological Sciences Research Council, UK Research & Innovation, National Institute of Health Research, Wellcome Sanger Institute. RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed, medRxiv, bioRxiv, Web of Science and Scopus for the terms (COVID-19 OR SARS-COV-2) AND (imported or importation) AND (sequenc* OR genom* or WGS). We filtered the 55 articles identified through this search and rejected any that did not undertake SARS-CoV-2 sequencing as part of an epidemiological investigation for importation into a different country. The remaining 20 papers were reviewed in greater detail to understand the patterns of importation and the methods used in each case. Added value of this studyThis is the first published study on importations of SARS-CoV-2 into England using genomics. Plessis et al., (2021) used a predictive model to infer the number of importations in to the UK from all SARS-CoV-2 genomes generated before 26th June 2020. The current study assesses the period 27/05/2020 to 13/09/2020 and presents findings of case-reported travel linked to genomic data. Two unpublished reports exist for Wales and Scotland, although only examine a comparatively small number of importations. Implications of all the available evidenceThis large-scale study has a number of findings that are pertinent to public health and of global significance, not available from prior evidence to our knowledge. The study demonstrates travel restrictions, through the implementation of travel-corridors, are effective in reducing the number of contacts per case based on observational data. Age has a significant effect on the number of contacts and this can be mitigated with travel restrictions. Analysis of divergent clusters indicates travel restrictions can reduce the number of onwards cases following a travel-associated case. Analysis of divergent clusters can allow for importations to be identified from genomics, as subsequently evidenced by cluster characteristics derived from contact tracing. The majority of importations of SARS-CoV-2 in England over Summer 2020 were from coastal European countries. The highest number of cases and onward contacts were from Greece, which was largely exempt from self-isolation requirements (bar some islands in September at the end of the study period). Systematic monitoring of imported SARS-CoV-2 cases would help refine implementation of travel restrictions. Finally, along with multiple studies, this study highlights the use of genomics to monitor and track importations of SARS-CoV-2 mutations of interest; this will be of particular use as the repertoire of clinically relevant SARS-CoV-2 variants expand over time and globally.

BackgroundSeverity of SARS-CoV-2 infection may vary over time. Here, we estimate age-specific risks of hospitalization, ICU admission and death given infection in the Netherlands from February 2020 to June 2021. MethodsA nationwide longitudinal serology study was used to estimate numbers of infections in three epidemic periods (February 2020 - June 2020, July 2020 - February 2021, March 2021 - June 2021). We accounted for reinfections and, as vaccination started in January 2021, breakthrough infections among vaccinated persons. Severity estimates were inferred by combining numbers of infections with aligned numbers of hospitalizations and ICU admissions from a national hospital-based registry, and aligned numbers of deaths based on national excess all-cause mortality estimates. ResultsIn each period there was a nearly consistent pattern of accelerating, almost exponential, increase in severity of infection with age. The rate of increase with age was highest for death and lowest for hospitalization. In the first period, the overall risk of hospitalization, ICU admission and death were 1.5% (95%-confidence interval [CI] 1.3-1.8%), 0.36% (95%-CI: 0.31-0.42%) and 1.2% (95%-CI: 1.0-1.4), respectively. The risk of hospitalization was higher in the following periods, while the risk of ICU admission remained stable. The risk of death decreased over time, with a substantial drop among [≥]70-years-olds in February 2021 - June 2021. ConclusionThe accelerating increase in severity of SARS-CoV-2 with age remained intact during the first three epidemic periods in the Netherlands. The substantial drop in risk of death among elderly in the third period coincided with the introduction of COVID-19 vaccination.

Analysing 92,598 variant screening tests performed on SARS-CoV-2 positive samples collected in France between 1 July and 31 August 2021 shows an increase of Kappa-like infections. Full genome sequencing reveals that these correspond to Delta variants bearing the S:E484Q mutation. Most of these sequences belong to a phylogenetic cluster and also bear the S:T95I mutation. Further monitoring is needed to determine if this trend is driven by undocumented superspreading events or an early signal of future viral evolutionary dynamics.

On February 27th, three cases of COVID-19 were reported among Norwegians that had recently returned from Lombardy, Italy. Travellers from the region rapidly became the most common source of imported infections in the earliest stage of the Norwegian COVID-19 epidemic. The situation was exacerbated by the unfortunate temporal overlap between the Norwegian winter holidays and intense epidemic spread of COVID-19 in Northern Italy, resulting in a large number of infected travellers. Here we combined flight data on travels between Norway and Lombardy with patient-level data to determine the fraction of travellers returning to Norway that had been infected with SARS-CoV-2. Travellers returning to Norway from Lombardy contracted COVID-19 at incidence rates up to 0.02 per person-day in the period spanning February 21st and March 1st, with a clear uptick in transmission in the middle of the period. This shows an example of the infection risk in tourist destinations being several fold higher than elsewhere in the region. In Norway, this is also supported by high rates of infections among tourists returning from Austria in February and March, despite a low number of reported cases in the country at the time. The massive COVID-19 prevalence among travellers suggest that mandatory quarantine of returning travellers or suspension of non-essential international flights is essential if the aim is to control or suppress the COVID-19 pandemic.

BackgroundThe Dutch government introduced the CoronaMelder smartphone application for digital contact tracing (DCT) to complement manual contact tracing (MCT) by Public Health Services (PHS) during the 2020-2022 SARS-CoV-2 epidemic. Modelling studies showed great potential but empirical evidence of DCT and MCT impact is scarce. MethodsWe determined reasons for testing, and mean exposure-testing intervals by reason for testing, using routine data from PHS Amsterdam (1 December 2020 to 31 May 2021) and data from two SARS-CoV-2 rapid diagnostic test accuracy studies at other PHS sites in the Netherlands (14 December 2020 to 18 June 2021). Throughout the study periods, notification of DCT-identified contacts was via PHS contact-tracers, and self-testing was not yet widely available. ResultsThe most commonly reported reason for testing was having symptoms. In asymptomatic individuals, it was having been warned by an index case. Only around 2% and 2-5% of all tests took place after DCT or MCT notification, respectively. About 20-36% of those who had received a DCT or MCT notification had symptoms at the time of test request. Test positivity after a DCT notification was significantly lower, and exposure-test intervals after a DCT or MCT notification were longer, than for the above-mentioned other reasons for testing. ConclusionsOur data suggest that the impact of DCT and MCT on the SARS-CoV-2 epidemic in the Netherlands was limited. However, DCT impact might be enlarged if app use coverage is improved, contact-tracers are eliminated from the digital notification process to minimise delays, and DCT is combined with self-testing. Author summaryDuring the 2020-2022 SARS-CoV-2 epidemic, the Dutch government introduced digital contact tracing (DCT) using a smartphone application to complement manual contact tracing (MCT) by professional contact-tracers. Mathematical models had suggested that DCT could slow down virus spread by identifying more individuals with whom the smartphone user had been in close contact and by reducing notification and testing delays after exposure. We used data collected during the Dutch epidemic to evaluate whether this was indeed the case and found that DCT and MCT had limited impact. Only around 2% of all tests took place after a DCT notification, and 2-5% after a MCT notification depending on MCT capacity at the time. Test positivity was lower after a DCT notification, and exposure-test intervals were longer after a DCT or MCT notification, than for other reasons for testing. About 20-36% of those who had received a DCT or MCT notification had symptoms at the time of test request and might have tested anyway even without having received the notification. However, DCT impact might be enlarged in future epidemics if app use coverage is improved and all exposure-notification-testing delays are minimised (e.g. no involvement of professional contact tracers and enabling self-testing after DCT notification).

The objective of this study was to estimate vaccine effectiveness (VE) against COVID-19 hospitalization and ICU admission, per period according to dominating SARS-CoV-2 variant (Alpha and Delta), per vaccine and per time since vaccination. To this end, data from the national COVID-19 vaccination register was added to the national register of COVID-19 hospitalizations. For the study period 4 April - 29 August 2021, 15,571 hospitalized people with COVID-19 were included in the analysis, of whom 887 (5.7%) were fully vaccinated. Incidence rates of hospitalizations and ICU admissions per age group and vaccination status were calculated, and VE was estimated as 1-incidence rate ratio, adjusted for calendar date and age group in a negative binomial regression model. VE against hospitalization for full vaccination was 94% (95%CI 93-95%) in the Alpha period and 95% (95%CI 94-95%) in the Delta period. The VE for full vaccination against ICU admission was 93% (95%CI 87-96%) in the Alpha period and 97% (95%CI 97-98%) in the Delta period. VE was high in all age groups and did not show waning with time since vaccination up to 20 weeks after full vaccination.

Italy is currently experiencing an epidemic of COVID-19 which emerged in the Lombardy region 1. During the interval between February 25-29, 2020, we identified 46 cases of COVID-19 reported in 21 countries in Europe, Africa, North America, and South America which were either in individuals with recent travel from Italy, or who had presumed infection by a traveler from Italy 2. In six cases, in four of the affected countries (Switzerland, France, Austria, Croatia), land travel was a likely route of introduction, or was documented to have been the route of introduction2.

Background During infectious disease outbreaks, characteristics of reported cases are routinely collected. These give information on becoming infected but not on infecting others. We assess whether linking infectees to infectors, together with their characteristics, can help understand transmission. Methods From the start of the COVID-19 pandemic in the Netherlands, reported cases were asked to identify their most probable infector in routine surveillance, enabling the linking of cases. We assess for the period 27 February 2020 - 11 April 2022 whether the infectees of these transmission pairs are representative of all reported cases, whether the transmission pairs yield verifiable estimates of epidemiological characteristics (here the serial interval), and whether they provide information on transmission that cannot be obtained otherwise. Results Of 8,003,008 reported cases, 678,482 (8.5%) could be linked to their most probable infector. These infectees were largely representative of the reported cases regarding age group, sex, and geographical location. The mean serial interval of 3.6 days (sd 3.4 days) from transmission pairs aligns with literature. Transmissions between age groups largely follow known contact patterns. Most transmissions in September 2021 occurred between persons who were not (fully) vaccinated, indicating the effectiveness of the vaccine, and relatively few between persons with different vaccination status, indicating assortative mixing in vaccination status. Conclusion Transmission pairs can be efficiently collected in routine surveillance, providing insight into disease transmission. The current post-pandemic period provides an excellent opportunity to adjust reporting systems for linking infectees to their most probable infector as preparation for future outbreaks.

BackgroundDecisions to impose temporary travel measures are less common as the global epidemiology of COVID-19 evolves. Risk-based travel measures may avoid the need for a complete travel ban, however evaluations of their effects are lacking. Here we investigated the public health effects of a temporary traffic light system introduced in the United Kingdom (UK) in 2021, imposing red-amber-green (RAG) status based on risk assessment. MethodsWe analysed data on international flight passengers arriving into Scotland, COVID-19 testing surveillance, and SARS-CoV-2 whole genome sequences to quantify effects of the traffic light system on (i) international travel frequency, (ii) travel-related SARS-CoV-2 case importations, (iii) national SARS-CoV-2 case incidence, and (iv) importation of novel SARS-CoV-2 variants. ResultsInternational flight passengers arriving into Scotland had increased by 754% during the traffic light period. Amber list countries were the most frequently visited and ranked highly for SARS-CoV-2 importations and contribution to national case incidence. Rates of international travel and associated SARS-CoV-2 cases varied significantly across age, health board, and deprivation groups. Multivariable logistic regression revealed SARS-CoV-2 cases detections were less likely among travellers than non-travellers, although increasing from green-to-amber and amber-to-red lists. When examined according to travel destination, SARS-CoV-2 importation risks did not strictly follow RAG designations, and red lists did not prevent establishment of novel SARS-CoV-2 variants. ConclusionsOur findings suggest that country-specific post-arrival screening undertaken in Scotland did not prohibit the public health impact of COVID-19 in Scotland. Travel rates likely contributed to patterns of high SARS-CoV-2 case importation and population impact.

We present early vaccine effectiveness (VE) estimates of the 2023 seasonal COVID-19 vaccination campaign using XBB.1.5 vaccine against COVID-19 hospitalization and ICU admission in previously vaccinated adults [≥]60 years old in the Netherlands. We compared vaccination status of 2050 hospitalizations including 92 ICU admissions with age group-, sex-, region- and date-specific population vaccination coverage between 9 October and 5 December 2023. VE against hospitalization was 70.7% (95% CI: 66.6; 74.3), VE against ICU admission was 73.3% (95% CI: 42.2; 87.6).

The rapid emergence of SARS-CoV-2 mutants with new phenotypic properties is a critical challenge to the control of the ongoing pandemic. B.1.1.7 was monitored in the UK through routine testing and S-gene target failures (SGTF), comprising over 90% of cases by March 2021. Now, the reverse is occurring: SGTF cases are being replaced by an S-gene positive variant, which we associate with B.1.617.2. Evidence from the characteristics of S-gene positive cases demonstrates that, following importation, B.1.617.2 is transmitted locally, growing at a rate higher than B.1.1.7 and a doubling time between 5-14 days. S-gene positive cases should be prioritised for sequencing and aggressive control in any countries in which this variant is newly detected. One-Sentence SummaryThe B.1.617.2 variant of SARS-CoV-2 is replacing B.1.1.7 and emerging as the dominant variant in England, evidenced by sustained local transmission.

BackgroundDespite the approval of BNT162b2 mRNA vaccine for children aged 6 months to 4 years by the European Medicines Agency (EMA) and the Federal Drug Administration (FDA) in 2022, no data on vaccine effectiveness (VE) of BNT162b2 are available in this age group. We here report on the VE of BNT162b2 during an Omicron BA.1-2 dominant period. MethodsAn authentication-based retrospective survey was performed between April 14th 2022 and May 9th 2022 in individuals that had registered children for off-label SARS-CoV-2 vaccination in Germany. We used Cox regression to estimate relative VE of two BNT162b2 doses, with the period between first and second vaccine dose as reference period (24.8+-0.6 days) and >=7 days after Dose 2 to before Dose 3 as post-vaccination period (59.5+-23.6 days). ResultsThe present analysis included 4615 children aged 2.8+-1.2 years (mean+-standard deviation) who had received their first dose of BNT162b2 on January 1st 2022 or thereafter. VE was substantial for protection from any SARS-CoV-2 infection (VE: 53.1% [95% confidence interval (CI): 36.3-69.6%], p<0.001), symptomatic SARS-CoV-2 infections (VE: 57.5% [95% CI: 40.8-74.2%], p<0.001), and SARS-CoV-2 infections leading to medication use (VE: 66.2% [95% CI: 43.7-88.7%], p<0.001). Differences in dosage of BNT162b2 yielded no change in VE. ConclusionThis study offers a first industry-independent insight in the potential VE of two doses of the BNT162b2 vaccine in children aged below 5 years, as currently only immunogenicity data by the manufacturer Pfizer/BioNTech are available. Limitations include the retrospective study design, and that the reported VE does not necessarily correspond to currently circulating SARS-CoV-2 variants.

We analyzed over 40 years of bacteriological surveillance data to reveal a 4-fold increase in Group A streptococcal (GAS) meningitis in 2022 compared to the annual average of 1982-2021 (n=5/year). Already 10 GAS meningitis cases occurred in 2023 (until March 13th). Molecular typing revealed that 25 out-of-29 (86%) isolates received in 2022 and 2023 were emm1.0 (Figure 1). WGS analysis of 19 emm1.0 isolates (2019 until 20th December 2022) demonstrated that 15 out-of-19 (79%) isolates belonged to the toxicogenic M1UK lineage. Based on these observations, we urge clinicians to be vigilant regarding clinical sign of meningitis with invasive GAS infections, since this disease manifestation appears to have a higher than expected occurrence due to clonal replacement by the recently-emerged M1UK variant. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/23286423v3_fig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@12ea749org.highwire.dtl.DTLVardef@1e8c4e6org.highwire.dtl.DTLVardef@d6dd1forg.highwire.dtl.DTLVardef@4f26dc_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1.C_FLOATNO Number of received S. pyogenes CSF isolates with proportion of emm1.0, 2013-2023 (until March 13th). C_FIG

In fall 2021 in Finland, the recommendation to use face masks in schools for pupils ages 12 years and above was in place nationwide. Some cities recommended face masks for younger pupils as well. Our aim was to compare COVID-19 incidence among 10-12-year-olds between cities with different recommendations on the use of face masks in schools. COVID-19 case numbers were obtained from the National Infectious Disease Registry (NIDR) of the Finnish Institute for Health and Welfare, where clinical microbiology laboratories report all positive SARS-CoV-2 tests with unique identifiers in a timely manner, including information such as date of birth, gender, and place of residence. The NIDR is linked to the population data registry, enabling calculation of incidences. We compared the differences in trends of 14-day incidences between Helsinki and Turku among 10-12-year-olds, and for comparison, also among ages 7-9 and 30-49 by using joinpoint regression. According to our analysis, no additional effect seemed to be gained from this, based on comparisons between the cities and between the age groups of the unvaccinated children (10-12 years versus 7-9 years).

COVID-19 is an emerging infectious disease which has been declared a pandemic by the World Health Organisation. Due to limited testing capacity for this new virus, variable symptomatology the majority of infected showing non-specific mild or no symptoms it is likely current prevalence data is an underestimate. MethodsWe present an estimate of the number of cases of COVID-19 compared to the number of confirmed case in Italy based on the daily reported deaths and information about the incubation period, time from symptom onset to death and reported case fatality rate. ResultsOur model predicts that on the 31st of January 2020 when the first 3 infected cases had been identified by Italian authorise there were already nearly 30 cases in Italy, and by the 24th of February 2020 only 0.5% cases had been detected and confirmed by Italian authorities. While official statistics had 132 confirmed case we believe a more accurate estimate would be closer to 26000. With a case-doubling period of about 2.5 days.

AimThe objective of this nationwide study was to investigate the association between SARS-CoV-2 transmissibility, viral load, and age of primary cases in Danish households. BackgroundSpread in households represents a major mode of transmission of SARS-CoV-2. In order to take proper action against the spread of the disease, it is important to have a better understanding of transmission in the household domain--including the role of viral load of primary cases. MethodsThe study was designed as an observational cohort study, using detailed administrative register data. We included the full population of Denmark and all SARS-CoV-2 tests (August 25, 2020 to February 10, 2021) to estimate transmissibility in house-holds comprising 2-6 people. RT-PCR Cycle threshold (Ct) values were used as a proxy for viral load. ResultsWe identified 63,657 primary cases and 139,882 household members of which 21% tested positive by RT-PCR within a 1-14 day period after the primary case. There was an approximately linear association between Ct value of the sample and transmissibility, implying that cases with samples having a higher viral load were more transmissible than cases with samples having a lower viral load. However, even for primary cases with relatively high sample Ct values, the transmissibility was not negligible, e.g., for primary cases with a sample Ct value of 38, we found that 13% of the primary cases had at least one secondary household case. Moreover, 34% of all secondary cases were found in households with primary cases having sample Ct values >30. An increasing transmissibility with age of the primary cases for adults ([&ge;]20 years) and a decreasing transmissibility with age for children (<20 years) were found. ConclusionsAlthough primary cases with sample high viral loads (low Ct values) were associated with higher SARS-CoV-2 transmissibility, we found no obvious cut-off for sample Ct values to eliminate transmissibility and a substantial amount of household transmission occurred in households where the primary cases had high sample Ct values (low viral load), The study further showed that transmissibility increases with age. These results have important public health implications, as they suggest that contact tracing should prioritize cases according to Ct values and age, and underline the importance of quick identification and isolation of cases. Furthermore, the study highlights that households can serve as a transmission bridge by creating connections between otherwise separate domains.

BackgroundDespite decades of vaccination whooping cough has not been eliminated and epidemics are known to occur every 3 to 5 years. As a consequence of the COVID-19 pandemic and associated non-pharmaceutical interventions, pertussis has been absent in 2020-2022. Many European countries have since seen large pertussis epidemics in 2023 and 2024. AimTo type Dutch pertussis isolates from 2023-2024 and compare these to pertussis isolates from 2015-2020. MethodsPertussis isolates received by the reference laboratory are routinely subjected to Illumina sequencing and genotyped. Expression of vaccine antigens and virulence factors was monitored over time (2015-2024). The 2023-2024 pertussis isolates were additionally typed using a cgMLST approach. ResultsBetween 2015-2020, 98% of isolates belonged to two dominant genotypes. Only 82% of 2023-2024 isolates belonged to these two genotypes, a third genotype was found to make up 13% of recent pertussis isolates. Fewer pertactin-deficient isolates were observed in 2023-2024, compared to isolates from 2015-2020. Furthermore, macrolide resistant isolates have not been detected, in contrast to reports by other European countries. Twenty-one recent isolates were found to contain a novel non-synonymous mutation in the type III secretion system translocator gene, bopD. ConclusionPertussis resurgence in the Netherlands coincided with the introduction of a third genotype, thereby resulting in increased genetic diversity when compared to isolates from 2015-2020. The third genotype is of the ancestral ptxP1 promoter type. A novel allele of the bopD gene has been identified, the implications of this mutation remain unclear at this time.

Since the emergence of Omicron, reinfections with SARS-CoV-2 have been rising. We estimated the risk of SARS-CoV-2 reinfection in the widely vaccinated French population, from January to August 2022. At nine weeks post-infection, the relative risk of reinfection, primary infection with pre-Delta variants being the reference group, was estimated at 0.43 [95%CI 0.40-0.47] if the primary infection was attributed to Delta, 0.21 [95%CI 0.19-0.24] with BA.1 and 0.17 [95% CI 0.15-0.18] with BA.2, and rapidly waned overtime. After a BA.1 primary infection the protection was similar against BA.2 or BA.4/5 reinfection.

Real-time dissemination of epidemiological survey data from positive COVID-19 cases is critical to support efforts to contain or reduce spread of viral infection in the community. Here we detected a significant association between domestic travel or travel to Europe and the identification of new cases in San Francisco, California, USA. These findings suggest that domestic and European travelers may need to be prioritized for evaluation of acute infection from COVID-19 in the setting of limited testing capacity.

Seroprevalence studies can contribute to better assess the actual incidence of infection. Since long-term data for Germany are lacking, we determined seroprevalence of IgG-antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 3,759 regular blood donors in three German federal states between July 2020 and June 2021. The IgG seroprevalence was 5.48% (95% confidence interval (CI): 4.77-6.25) overall, ranging from 5.15% (95% CI: 3.73-6.89) in Lower Saxony to 5.62% (95% CI: 4.57-6.84) in North Rhine Westphalia.